Preeclampsia is a syndrome defined by pregnancy-induced hypertension and proteinuria, which can lead to eclampsia (convulsions), and other serious maternal and/or fetal complications. Preeclampsia is originated in early gestation from the failure of implantation mechanisms and/or placental development, and is thus closely related to complications of pregnancy in early gestation such as including but not limited to implantation failure, and threatened and spontaneous miscarriage, Preeclampsia affects approximately 5-7% of pregnant women (approximately 8,370,000 pregnant women worldwide per year) and is a major cause of maternal and perinatal mortality. Furthermore, women with preeclampsia have an 8-fold higher risk of cardiovascular death later in their life, and offspring born from pregnancies affected by preeclampsia have an increased risk of metabolic and cardiovascular disease and mortality later in life.
The present diagnostic criteria for preeclampsia set by the United States National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy include new-onset hypertension coupled with proteinuria that develops after 20 weeks of gestation in women with previously normal blood pressures. These criteria further define preeclampsia as systolic or diastolic blood pressures of ≥140 and/or ≥90 mmHg, respectively, measured at two or more different time points, at least 4 hours (h) but not more than 1 week apart, as well as proteinuria of ≥300 mg protein in a 24 h urine sample, or two random urine specimens obtained at least 4 h but not more than 1 week apart containing ≥1+ protein on a dipstick.
Based on the timing of the clinical manifestation, preeclampsia has been historically classified into different sub-forms, such as “term” (≥37 weeks) and “preterm” (<37 weeks) or by using an alternative terminology “late-onset” and “early-onset” preeclampsia. The latter classification has not been uniformly used, but different studies have employed a range of gestational age cutoffs varying between 28 and 35 weeks for the distinction between early-onset and late-onset preeclampsia. Recently, it has been suggested to define 34 weeks as the gestational age cutoff between these two forms. It is important to note that preeclampsia may occur intrapartum or postpartum; thus, monitoring and evaluating the symptoms of preeclampsia should be continued during the postpartum period.
In 1954, it was first reported that preeclampsia may be associated with haemolysis, abnormal liver function and thrombocytopenia. Initially accepted to be a severe variant of preeclampsia, this group of symptoms later was suggested to constitute a separate clinical entity termed Haemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome. Supporting the idea that HELLP syndrome is a distinct condition, up to 20% of HELLP syndrome patients do not develop hypertension, 5-15% have minimal or no proteinuria and 15% show neither hypertension nor proteinuria. Moreover, laboratory findings in HELLP syndrome rarely correlate with the severity of hypertension or proteinuria.
In addition to the medical complications suffered by mothers and risks to the offspring, preeclampsia and HELLP syndrome cause approximately $7 billion in healthcare costs in the United States annually. Accordingly, there have been many attempts to provide a reliable predictive test for preeclampsia/HELLP syndrome. Previous attempts have involved assays for the concentrations of circulating biochemical markers in maternal blood but to date, the scientific literature on these approaches have been contradictory and inconclusive. There is a need in the art for new and improved methods of predicting and diagnosing these conditions.